Though current vaccines reduce the impact of influenza, IAV remains a major human pathogen with an enormous global and domestic impact, causing 30,000 deaths and economic costs totaling tens of billions dollars each year in the USA. Despite its remarkable impact on public health, we have only a limited understanding of the molecular mechanisms underlying viral pathogenesis and its ability to evade the immune response. In this project we are studying a number of aspects of the interaction between IAV and the host. Most of studies utilize the mouse model of infection. Our interests include understanding selection of antigenic variants in vivo, the interaction between the nervous and immune systems in regulating anti-viral immunity, and the role of the PB1-F2 protein in viral pathogenesis. We found that PB1-F2 enhances influenza A virus pathology as well as the additional pathology.